Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial

作者：Hideaki Bando, Jun Watanabe, Yusuke Takahashi, Masahito Kotaka, Nobuhisa Matsuhashi, Eiji Oki, Yoshito Komatsu, Manabu Shiozawa, Keiji Hirata, Yuji Miyamoto, Masanobu Takahashi, Kentaro Yamazaki, Dai Manaka, Akiyoshi Kanazawa, Yi-Hsin Liang, Kun‐Huei Yeh, Yuko Watsuji, Yuko Yamamoto, Makoto Fukui, Shruti Sharma, Vasily N. Aushev, Adham Adel Jurdi, Matt Rabinowitz, Minetta C. Liu, Alexey A. Aleshin, Ichiro Takemasa, Daisuke Kotani, Akihiro Sato, Toshihiro Misumi, Yoshiaki Nakamura, Qian Shi, Hiroya Taniguchi, Takayuki Yoshino, Takeshi Kato · 发表于：Nature Medicine · 年份：2026 · DOI：10.1038/s41591-026-04428-0 · 被引用次数：7 · 研究领域：Cancer Genomics and Diagnostics、Colorectal Cancer Treatments and Studies、Cancer Cells and Metastasis

Tumor-informed circulating tumor DNA (ctDNA) enables detection of molecular residual disease (MRD) after curative resection of colorectal cancer (CRC), but whether early intervention improves outcomes remains uncertain. ALTAIR was a randomized, double-blind, phase 3 trial embedded in the CIRCULATE-Japan platform evaluating a post-adjuvant ctDNA surveillance strategy with treatment initiation upon molecular recurrence. Patients with resected stage 0–IV CRC who became ctDNA positive after completion of standard-of-care therapy and had no radiological evidence of disease were randomly assigned (1:1) to receive trifluridine/tipiracil (FTD/TPI) or placebo for 6 months. The primary endpoint was investigator-assessed disease-free survival (DFS). Between July 2020 and June 2023, 243 patients were randomized to FTD/TPI (n = 122) or placebo (n = 121). Median DFS was 9.30 months with FTD/TPI and 5.55 months with placebo (hazard ratio = 0.79, 95% confidence interval: 0.60–1.05, P = 0.107), and the primary endpoint was not met. FTD/TPI increased grade 3 or higher hematologic adverse events (73.0% versus 3.3%) without new safety signals. These findings indicate that post-adjuvant intervention with FTD/TPI did not significantly improve DFS in ctDNA-positive patients without radiological disease. ClinicalTrials.gov identifier: NCT04457297 . In the randomized, double-blind phase 3 ALTAIR trial, patients with resected colorectal cancer who became positive for circulating tumor DNA during post-...